The objective of this study is to characterize quantitatively the processes underlying the generation of action potentials in vertebrate motoneurons and to explore the regulation of those processes. Preliminary data show that the membrane properties of frog and cat motoneurons are considerably different from those of the extensively studied squid giant axon and frog node of Ranvier; but that the basic concept of voltage-dependent ionic permeability changes applies to the major currents contributing to motoneuron action potentials. Since the membrane properties of motoneuron dendrites are likely to be different from those of the soma, measurements will be made on small localized membrane regions. Using the visual feedback possible with neurons grown in monolayer tissue culture, electrodes will be placed in various regions of the neuron to provide local control over membrane voltage. Currents from the small patches of membrane under good voltage clamp control will be measured by local current density and 'spot clamp' methods. The various voltage dependent ionic currents will be separated and measured using agents that block specific currents (TTX, TEA) and by changing the concentrations of the external ions that are suspected to be current carriers (Na ion, K ion, Ca ions, C1). The experiments on neurons grown in tissue culture will be complimented and checked by experiments on tissue slices acutely removed from the spinal cord and by in vivo experiments. The experimental data will be used to reconstruct as far as possible the translation of synaptic inputs into action potential frequency by motoneurons and to understand the relation between changes in the basic membrane processes and deviations in motoneuron function.